Who will lose weight on sibutramine and orlistat? Psychological correlates for treatment success

Aim:  To study the associations between weight loss with sibutramine and orlistat with psychological aspects that may interact with patients' response to these drugs.
Methods:  A total of 478 obese patients with a mean body mass index of 42 ± 12 kg/m² gave self-reported, retrospective data on different types of previous weight loss treatments (sibutramine and orlistat, and Weight Watchers used as a control condition) including the amount of weight lost with these treatments, eating behaviour (Dutch Eating Behaviour Questionnaire) and personality (NEO Personality Inventory – Revised).
Results:  Greater weight loss with sibutramine was associated with lower levels of restrained eating and higher levels of 'neuroticism', in particular 'anxiety' and 'depression'. Greater weight loss with orlistat was associated with aspects of the personality dimension 'conscientiousness' (e.g. 'order' and 'deliberation').
Conclusion:  Sibutramine may exert its greatest effect in patients whose eating is a 'natural' response to hunger rather than regulated by cognitions and conscious controls. Patients with low levels of restraint could be more sensitive to the satiety-enhancing effect of sibutramine. They may be able to reduce their food intake without cognitive interference and/or start to control their eating most radically in response to enhanced satiety. Enhanced satiety may also help patients withstand a wish to eat triggered by psychological distress. Possible central nervous system effects on mood could also have reduced eating, which was related to distress. The administration regimen of orlistat is more demanding, requiring greater adherence. This can account for the finding that personality attributes such as conscientiousness are important for success.     

NIA0005Long-term weight maintenance: does diet composition matter? A randomized, prospective trial

Background:  High protein diets confer weight loss and metabolic advantages over high carbohydrate diets in the short-to-medium term. Little has been published on long-term use of high protein diets, especially in the context of weight maintenance following significant weight loss.
Methods:  The study consisted of two phases. The first phase saw patients provided with a very low energy diet for 12 weeks. Patients who lost > 10% of their body weight progressed to the second phase in which they were randomly allocated to a high carbohydrate (HC) (55% carbohydrate) or high protein (HP) diet (30% protein) to maintain their weight loss. Patients were followed up monthly for 12 months. Anthropometric and cardiovascular risk factors were measured.
Results:  A total of 173 overweight or obese people (88 males, 85 females) aged 43 years (SD = 10.6); weight 112.2 kg (±24.6); Body Mass Index 39.2 kg/m² (±7.7) were enrolled. 151 patients (87.3%) completed phase I and entered phase II. There was no significant difference between the weight loss recorded during phase I for each group after randomization (mean weight loss 18.5 kg ±6.9 kg and 17.7 ± 5.0 respectively). On average, patients from both groups were reasonably successful in maintaining their weight loss at completion of phase II (HC 14.7 ± kg 12.5 vs. HP 14.8 kg ± 9.7), with no significant difference between the groups.
Conclusion :   Although a high protein diet compares favourably to a high carbohydrate diet in the short-to-medium term, in this study a high protein diet exhibited no advantage over a higher carbohydrate diet in achieving weight maintenance over a 12 month period.     

Associates of change in liver fat content in the morbidly obese after laparoscopic gastric banding surgery

Aim:  Hepatic steatosis affects up to 30% of the population. After weight loss, monitoring of the change in hepatic steatosis is not routinely performed. This study aimed to define the closest associates of change in liver fat content in a population of obese females following laparoscopic gastric banding surgery.
Methods:  Before and 3 months after surgery, proton magnetic resonance spectroscopy and magnetic resonance imaging were used to estimate the amount of lipid contained within the liver and abdominal subcutaneous and visceral compartments of 29 obese [mean body mass index (BMI) 39 ± 5 kg/m²], non-diabetic women aged between 20 and 62 years. Liver enzymes, fasting plasma glucose and insulin were also measured as well as body weight, BMI and waist circumference. Insulin sensitivity was estimated using homeostasis model assessment insulin resistance index.
Results:  Significant reductions occurred in body weight (p < 0.001), abdominal fat volumes (p < 0.001) and liver fat (p = 0.037) 3 months after surgery. Change in liver fat content more closely associated with change in serum gamma-glutamyl transferase (GGT; r = 0.71, p < 0.001) than with changes in weight (r = 0.10, p = 0.612) and waist circumference (r = 0.15, p = 0.468).
Conclusions:  Our findings suggest that obese non-diabetic female patients who have undergone significant weight loss over 3 months can be better assessed for the regression of excess liver fat content by monitoring changes in serum GGT levels rather than changes in simple anthropometry.     

Impact of weight loss on the metabolic syndrome

Aim: Individuals with the metabolic syndrome (MS), a clustering of risk factors [triglycerides, glucose, high-density lipoprotein cholesterol, blood pressure (BP), abdominal obesity] defined by the National Cholesterol Education Program (NCEP), are at high risk for coronary heart disease and type 2 diabetes mellitus, and may benefit from aggressive lifestyle modification.
Methods: We reviewed 1 year of consecutive patients' charts to determine the prevalence of the MS in obese individuals enrolled in a medically supervised rapid weight loss programme, the correlation of weight change with the components of the MS, and response to diet-induced weight loss.
Results: Out of 185 individuals, 125 (68%) met the NCEP definition of the MS. A moderate decrease in weight (6.5%) induced by a very low calorie diet (VLCD) resulted in substantial reductions of systolic (11.1 mmHg) and diastolic (5.8 mmHg) blood pressure (BP), glucose (17 mg/dl), triglycerides (94 mg/dl) and total cholesterol (37 mg/dl) at 4 weeks (all p < 0.001). These improvements were sustained at the end of active weight loss (average 16.7 weeks; total weight loss 15.1%), with further significant reductions in BP and triglycerides. Weight loss was related to the changes in each criterion of the metabolic syndrome.
Conclusions: The MS is prevalent in two-thirds of obese individuals enrolling in a structured weight loss programme. Moderate weight loss with a VLCD markedly improved all aspects of the MS.     

Preoperative and post‐operative psychosocial interventions for bariatric surgery patients: A systematic review

Psychosocial interventions are increasingly being utilized to help patients prepare for, and adjust to changes following, bariatric surgery in order to optimize psychosocial adjustment and weight loss. The current systematic review examined the impact of preoperative and post‐operative psychosocial interventions with a behavioural and/or cognitive focus on weight, dietary behaviours, eating pathology, lifestyle behaviours, and psychological functioning. A PsycINFO and Medline search of publications was conducted in March 2019. Two authors assessed retrieved titles and abstracts to determine topic relevance and rated the quality of included studies using a validated checklist. Forty‐four articles (representing 36 studies) met the study inclusion criteria. The current evidence is strongest for the impact of psychosocial interventions, particularly cognitive behavioural therapy, on eating behaviours (eg, binge eating and emotional eating) and psychological functioning (eg, quality of life, depression, and anxiety). The evidence for the impact of psychosocial interventions on weight loss, dietary behaviours (eg, dietary intake), and lifestyle behaviours (eg, physical activity) is relatively weak and mixed. Psychosocial interventions can improve eating pathology and psychosocial functioning among bariatric patients, and the optimal time to initiate treatment appears to be early in the post‐operative period before significant problematic eating behaviours and weight regain occur.     

Effects of metformin on peripheral insulin sensitivity and intracellular lipid contents in muscle and liver of overweight Japanese subjects

Aim:  Recent studies suggest that insulin resistance is associated with increased intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) contents. While metformin improves insulin resistance mainly in liver, its effects on IHL and IMCL have not been clarified yet. The aim of this study was to investigate the effects of low-dose metformin (750 mg/day) on peripheral insulin sensitivity, IHL and IMCL.
Methods:  Before and 3 months after low-dose metformin therapy, eight overweight/obese Japanese subjects [body mass index (BMI) >25 kg/m²] were studied with blood sampling, measurement of IHL and IMCL by ¹H magnetic resonance spectroscopy and glucose infusion rate (GIR) during euglycaemic–hyperinsulinaemic clamp as an index of peripheral insulin sensitivity.
Results:  A 3-month low-dose metformin therapy did not alter body weight, total body fat, fat distribution or physical activity level but increased GIR by 31% (from 6.24 ± 0.86 to 7.82 ± 0.82 mg/kg/min, p < 0.01). Although metformin treatment did not alter IMCL (from 4.1 ± 1.0 to 4.2 ± 0.9, not significant), it decreased IHL by 21% (from 15.9 ± 2.8 to 11.8 ± 2.2%, p < 0.05).
Conclusions:  A 3-month low-dose metformin treatment improved peripheral insulin sensitivity and reduced IHL, without significantly changing BMI, adiposity or IMCL.     

Sibutramine enhances insulin sensitivity ameliorating metabolic parameters in a double-blind,randomized, placebo-controlled trial

Aim:  To assess the effect of sibutramine-assisted weight reduction program on insulin sensitivity and metabolic parameters in obese normal glucose tolerant individuals over a period of 24 weeks.
Research Design and Methods:  A double-blind, placebo-controlled, parallel, prospective clinical trial was carried out at our medical centre. Forty female normal glucose tolerant patients, body mass index: 34.3 ± 2.9 kg/m² and age: 41.1 ± 9.9 (range: 19–58 years), were randomized to placebo or sibutramine, 10 mg once daily.
Results:  Seventeen patients from sibutramine group and 14 placebo had completed the study protocol. Significant weight change was seen in sibutramine (p < 0.01) (−5.6 kg or −6.1% vs. +0.9 kg or +1.1% in placebo). Insulin sensitivity enhanced in sibutramine group ( K _itt: from 4.03 ± 1.97 to 5.09 ± 2.48%/min; p < 0.05). Homeostasis model assessment-IR (HOMA-IR) decreased from 7.8 ± 6.9 to 5.6 ± 4.5 (p < 0.05). HOMA-β also decreased from 508 ± 381 to 374 ± 256 (p < 0.05). No changes were observed in the placebo control group regarding insulin sensitivity or secretion. Concomitant reductions were observed in the sibutramine group in lipid parameters (triglycerides and high-density lipoprotein-cholesterol), uric acid and gamma-glutamyl transferase (p < 0.05).
Conclusions:  Sibutramine has demonstrated efficacy in reducing weight in non-diabetic women along with amelioration in insulin sensitivity and additional improvement in metabolic parameters.     

The effects of Xanthigen™ in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat

Aim: To investigate the effects of Xanthigen (brown marine algae fucoxanthin + pomegranate seed oil (PSO)) on body weight, body fat, liver lipids, and blood biochemistry; and Xanthigen and its individual components on resting energy expenditure (REE) in obese, non-diabetic female volunteers with non-alcoholic fatty liver disease (NAFLD) and normal liver fat (NLF) content.
Methods: Sixteen-week, double-blind, randomized, placebo-controlled study. Food record data, body composition, REE (only 41 volunteers with NAFLD) and blood sample analysis were assessed weekly for 16 weeks in 151 non-diabetic, obese premenopausal women with liver fat content above 11% (NAFLD) n = 113, and below 6.5% (NLF) n = 38.
Results: Xanthigen-600/2.4 mg (300 mg PSO + 300 mg brown seaweed extract containing 2.4 mg fucoxanthin) resulted in statistically significant reduction of body weight (5.5 ± 1.4 kg NAFLD group and 4.9 ± 1.2 kg NLF group, p < 0.05), waist circumference (NAFLD group only), body (3.5 ± 1.9 kg NAFLD group, p < 0.001; 3.6 ± 0.7 kg NLF group, p < 0.05) and liver fat content, liver enzymes (NAFLD group only), serum triglycerides and C-reactive protein. Weight loss and reduction in body and liver fat content occurred earlier in patients with NLF than in patients with NAFLD. Fucoxanthin ( > 2.4 mg) and Xanthigen-400/1.6 mg (200 mg PSO + 200 mg brown seaweed extract containing 1.6 mg fucoxanthin) significantly increased REE in NAFLD subjects compared to placebo.
Conclusions: Xanthigen promoted weight loss, reduced body and liver fat content, and improved liver function tests in obese non-diabetic women. Xanthigen and Fucoxanthin also increased REE. This product may be considered a promising food supplement in the management of obesity.     

Cognitive appraisals of dietary transgressions by obese women: associations with self-reported eating behavior, depression, and actual weight loss

OBJECTIVE: To identify three groups of obese people entering weight loss treatment, who have distinctly different cognitive appraisals of dietary transgressions and to compare these groups on self-report inventories of eating patterns, dieting, and depression, as well as on treatment completion rates and weight loss. DESIGN: Retrospective review of clinical records. Using a measure which evaluates eating-related cognitive appraisals, participants were categorized into one of three cognitive groups (All-or-None, Rationalization, Matter-of-Degree). SUBJECTS: 289 treatment-seeking obese women (age: 40.9 y, body mass index (BMI): 34.7 kg/m2). MEASUREMENTS: Self-reported eating and dieting behavior (Three-Factor Eating Questionnaire and Eating Behavior Inventory); depression (Beck Depression Inventory); attendance information and body weight obtained during treatment. RESULTS: The cognitive group representing objective thinkers (Matter-of-Degree) reported significantly fewer problems with overeating and more personal control over eating than did the rigid, dichotomous thinkers (All-or-None). In addition, the Matter-of-Degree (MAT) group endorsed significantly less subjective hunger and fewer depressive symptoms than the other two cognitive groups. The Rationalization group was more likely to complete a treatment program than was the All-or-None group, with the MAT group not differing from either. Despite these findings, there were no significant differences among cognitive groups on total weight loss. CONCLUSIONS: Cognitive appraisals of weight-control lapses appear to be associated with self-reported eating behavior, depressive symptoms and treatment completion rates, but not with treatment-induced weight loss. The relationship between long-term weight loss and cognitive appraisals of dieting lapses is yet to be determined. It appears necessary to assess empirically the validity of assumptions regarding factors associated with treatment outcome.     

Effect of metformin, orlistat and pioglitazone treatment on mean insulin resistance and its biological variability in polycystic ovary syndrome

Context  Mean insulin resistance (IR) is greater and it is also more variable in overweight women with polycystic ovarian syndrome (PCOS) compared to weight matched controls. Whilst treatment will reduce the mean IR, it is not known if the IR variability is also reduced.
Objective  To compare the change in IR and its variability before and after treatment with insulin sensitization through metformin and pioglitazone, compared to that induced by weight loss with orlistat.
Design  Randomized, open labelled parallel study.
Setting  Endocrinology outpatient clinic at a referral centre.
Patients  Thirty obese PCOS patients [BMI 36·0 ± 1·2 kg/m² (mean ± SEM)] participated in the study.
Intervention  The change in biological variability (BV) was assessed by measuring IR (homeostasis model assessment method) at 4-day intervals on 10 consecutive occasions before and 12 weeks after randomization to metformin, pioglitazone or orlistat.
Outcome measured  The primary end point of the study was a change in BV of IR.
Results  Treatment with pioglitazone, orlistat and metformin reduced the overall IR by 41·0 ± 4·1%, 19·7 ± 6·4% and 16·1 ± 6·8% ( P =  0·005, P  = 0·013, P  = 0·17, respectively) and IR variability by 28·5 ± 18·0%, 41·8 ± 11·6% and 23·7 ± 17·0 ( P =  0·20, P  = 0·015 and P  = 0·28, respectively). Free androgen index reduced significantly with all treatments.
Conclusion  Only orlistat reduced both IR and its variability significantly, though all three drugs were effective in reducing hyperandrogenism within the 12-week period of the study.     

Do baseline serum leptin levels predict weight regain after dieting in obese women?

SUMMARY
Aim   Weight loss achieved during weight reduction programme is difficult to maintain. We investigated the possible role of circulating leptin in failure or success in maintaining weight loss.
Methods   Serum leptin levels were measured in 30 healthy premenopausal obese women before and after 12 weeks of dietary intervention and after 5 months of follow-up.
Results   After intervention body mass index (BMI) decreased from 30.6 to 25.4 kg/m² (p < 0.01) and leptin levels decreased from 16.7 to 7.7 ng/ml (p < 0.01). After 5 months follow-up 12 women regained reduced weight and 18 women maintained weight loss. In the regainers leptin levels increased again, but remained low in the maintainers. Baseline leptin concentrations were lower in the regainers than in the maintainers (12.1 vs. 21.2 ng/ml, p = 0.04). During intervention leptin levels decreased three times more in the maintainers than in the regainers, although weight loss was similar in both groups.
Conclusions   This study shows that obese women who regain weight after dieting have significantly lower baseline leptin levels than women who maintain weight loss. Our results suggest that differences in leptin resistance might exist in similarly obese women which could influence the success of dieting.     

Inflammatory biomarkers and physical function in older, obese adults with knee pain and self-reported osteoarthritis after intensive weight-loss therapy

OBJECTIVES: To describe the relationships between proinflammatory biomarkers and self-reported and performance-based physical function and to examine the effect of weight loss on these markers of inflammation.
DESIGN: Randomized, longitudinal, clinical study comparing subjects eating an energy-restricted diet and participating in exercise training with a control group.
SETTING: Community-base participants for the Physical Activity, Inflamation and Body Composition Trial.
PARTICIPANTS: Eighty-seven obese (body mass index (BMI) >30.0 kg/m²) adults aged 60 and older with knee pain and self-report of osteoarthritis.
MEASUREMENTS: Inflammatory biomarkers (interleukin 6 (IL-6), tumor necrosis factor alpha (TNFα), C-reactive protein, and soluble receptors for TNFα (sTNFR1 and sTNFR2)) and self-reported (Western Ontario and McMaster University Osteoarthritis Index questionnaire) and performance-based (6-minute walk distance and stair climb time) measures of physical function at baseline and 6 months.
RESULTS: Mean (standard error of the mean) weight loss was 8.7% (0.8%) in the intervention group, compared with 0.0% (0.7%) in the control group. sTNFR1 was significantly less in the intervention group than in the control group at 6 months. sTNFR1 and sTNFR2 predicted stair climb time at baseline. Change across the 6-month intervention for sTNFR2 was an independent predictor for change in 6-minute walk distance.
CONCLUSION: These results indicate that an intensive weight-loss intervention in older obese adults with knee pain can help improve inflammatory biomarkers and that changes in these concentrations showed associations with physical function.     

Expression of adiponectin and its receptors in livers of morbidly obese patients with non-alcoholic fatty liver disease

Background and Aim:  Obesity is one of the risk factors for non-alcoholic fatty liver disease (NAFLD) and a common disease that comprises simple steatosis and non-alcoholic steatohepatitis (NASH), and can eventually lead to liver cirrhosis. Adiponectin is an adipocyte-derived protein that has anti-obesity, antidiabetic and anti-inflammatory properties, and is considered to possess a hepatoprotective function. Its role in the development and progression of NAFLD in morbidly obese patients is unknown. In this study, we examined the expression levels of adiponectin and its receptors in liver biopsies of morbidly obese patients and then determined whether there was an association with the disease severity.
Methods:  Liver biopsies from 30 morbidly obese patients (18 NASH vs 12 steatosis) were analyzed. The needle core biopsies were subjected to routine histological examination and stained immunohistochemically for adiponectin, adiponectin receptor I (adipoRI) and receptor II (adipoRII).
Results:  The two groups were comparable with respect to body mass index, age and gender distribution. The expression of adiponectin decreased in liver biopsies with NASH as compared to those with simple steatosis (1.61 ± 0.70 vs 2.25 ± 0.75, P  = 0.028). Spearman's rank correlation coefficient analysis showed that the staining intensity of adiponectin negatively correlated with the grade of inflammation ( r  = −0.368, P  = 0.045) and stage of fibrosis ( r  = −0.380, P  = 0.038). There was no significant difference in expression of adipoRI and adipoRII between the two groups.
Conclusion:  These findings indicate that decreased liver adiponectin expression may play a role in the development and progression of NAFLD, from simple steatosis to NASH, in morbidly obese patients.     

Prevention of weight gain in type 2 diabetes requiring insulin treatment

Background: Patients with type 2 diabetes who are failing on oral agents will generally gain a large amount of body fat when switched to insulin treatment. This adverse effect may be related to chronic hyperinsulinism induced by long-acting insulin compounds.
Aim: To test the concept that regain of glycaemic control can be achieved without causing weight gain, using a regimen free of long-acting insulin.
Methods: In a 3-month open-label pilot study including 25 patients with moderate overweight and secondary failure, we investigated whether nocturnal glycaemic control could be achieved with glimepiride administered at 20:00 hours. The starting dose was 1–2 mg, with subsequent titration up to a maximum of 6 mg. Rapid-acting insulin analogues were used three times daily to regain postprandial glucose control.
Results: Glycaemic control at 3 months was established with glimepiride in a dose of 4.4 ± 0.3 mg/day (mean ± standard error of the mean), and a total daily insulin dose of 24.1 ± 2.6 IU. Fasting glucose levels decreased from 12.7 ± 0.6 mmol/l to 8.1 ± 0.3 mmol/l (p  <  0.001), and target levels were reached in 14 of 25 patients (56%). Mean HbA1c decreased from 10.5 ± 0.4 to 7.7 ± 0.2% (p  <  0.001). Symptomatic nocturnal hypoglycaemia was not reported. Body weight did not change (85.7 ± 3.6 kg vs. 85.7 ± 3.3 kg, p = 0.99).
Conclusion: The data suggest that this new approach may be useful in about 50% of type 2 diabetes patients presenting with failure on maximal oral treatment.     

Usefulness of troglitazone administration to obese hyperglycaemic patients with near-normoglycaemia

Aims:   We assessed the effectiveness of 400 mg/day of troglitazone administered to hyperglycaemic patients with near-normoglycaemia who were obese and who had hyperinsulinaemia.
Results:   The area under the plasma glucose curve in oral glucose tolerance tests (OGTT) significantly decreased from 39.8 ± 19.4–20.5 ± 10.2 mg/dL · h and the area under the insulin-response curve from 31.8 ± 22.5–12.2 ± 5.7 μU/ml · h 4 months after the start of treatment. The level of HbA1c significantly improved from 6.6 ± 0.2 to 6.3 ± 0.2% (p < 0.05) by 1 month after administration, and that of serum 1,5-anhydroglucitol (1,5-AG) from 12.6 ± 1.1–18.3 ± 2.5 μ/ml (p < 0.05). In some cases, recovery of the first-phase insulin secretion was observed.
Conclusions:   These findings suggest that the administration of this insulin sensitizer is useful in the treatment of obese Japanese subjects with borderline or mild diabetics accompanied by hyperinsulinaemia.     

The effect of acarbose on insulin resistance in obese hypertensive subjects with normal glucose tolerance: a randomized controlled study

Aim:  Acarbose, a glucose oxidase inhibitor, delays the absorption of glucose thus reducing post-prandial blood glucose level, haemoglobin A1c (HbA1c) and insulin resistance in patients with diabetes mellitus and in subjects with impaired glucose tolerance. The effect of acarbose in subjects with normal glucose tolerance (NGT) has hitherto not been examined. The aim of the present study was to examine the effect of acarbose in obese hypertensive subjects with NGT.
Methods:  A double-blinded, parallel group study was performed on 56 male subjects with hypertension, body mass index (BMI) 27–35 kg/m², fasting blood glucose ≤ 6 mmol/l and a normal oral glucose tolerance test. Blood pressure, HbA1c, lipid profile and insulin resistance [homeostasis model assessment (HOMA) index] were determined initially and following 24 weeks of acarbose, 150 mg/day or placebo. The primary end point was the change in insulin resistance. Anti-hypertensive treatment and diet were kept constant during the study.
Results:  Insulin resistance decreased in acarbose users but not on placebo. HOMA index declined from 5.36 ± 1.7 to 4.10 ± 1.6 (p = 0.001) on acarbose, the corresponding values on placebo were 5.44 ± 1.9 and 5.53 ± 1.7. A decrease in serum triglyceride values (2.16 ± 0.16 mmol/l to 1.76 ± 0.15 mmol/l, p = 0.02) took place on acarbose with no change on placebo. There was no change in BMI, low-density lipoprotein or high-density lipoprotein values in either group. Blood pressure declined equally in both the groups, probably due to better patient compliance.
Conclusions:  Acarbose may reduce insulin resistance and triglycerides also in obese hypertensive subjects with normal glucose tolerance.     

Improved glycaemic control decreases inner mitochondrial membrane leak in type 2 diabetes

Aim:  Several mechanisms have been targeted as culprits of weight gain during antihyperglycaemic treatment in type 2 diabetes (T2DM). These include reductions in glucosuria, increased food intake from fear of hypoglycaemia, the anabolic effect of insulin, decreased metabolic rate and increased efficiency in fuel usage. The purpose of the study was to test the hypothesis that mitochondrial efficiency increases as a result of insulin treatment in patients with type 2 diabetes.
Methods:  We included ten patients with T2DM (eight males) on oral antidiabetic treatment, median age: 51.5 years (range: 39–67) and body mass index (BMI): 30.1 ± 1.2 kg/m² (mean ± s.e.). Muscle biopsies from m. vastus lateralis and m. deltoideus were obtained before and after seven weeks of intensive insulin treatment, and mitochondrial respiration was measured using high-resolution respirometry. State 3 respiration was measured with the substrates malate, pyruvate, glutamate, succinate and ADP. State 4o was measured with addition of oligomycine. An age, sex and BMI-matched control group was also included.
Results:  HbA1c improved significantly and the patients gained on average 3.4 ± 0.9 kg. Before treatment, respiratory control ratios (RCRs) of the T2DM were lower than the obese controls [2.6 vs. 3.2 (p < 0.05)], but RCR returned to the levels of the control subjects during treatment. Average state 4o of arm and leg declined by 14% (p < 0.05) during insulin treatment.
Conclusions:  Tight glycaemic control leads to reductions in inner mitochondrial membrane leak and increased efficiency of mitochondria. This change in mitochondrial physiology could contribute to the weight gain seen with antihyperglycaemic treatment.     

Smoking cessation and glycaemic control in type 2 diabetic patients

Aim:  To elucidate the relationship between glycaemic control, blood pressure and body-weight change after smoking cessation in type 2 diabetic patients.
Methods:  We examined HbA_1c, blood pressure and body weight in 15 type 2 diabetic patients before, 6 and 12 months after quitting smoking. Sixteen type 2 diabetic patients who did not quit smoking served as control.
Results:  Body weight slightly increased after quitting smoking. Although HbA_1c levels showed no change in the control group, those in patients who quit smoking significantly increased (6.8 ± 0.3% before quitting smoking; 7.4 ± 0.3% 6 months after quitting smoking, p < 0.05; 7.8 ± 0.4% 12 months after quitting smoking, p < 0.001). Fasting blood glucose also increased in patients who quit smoking. The increase in body weight after quitting smoking did not correlate with the deterioration of glycaemic control. Diastolic blood pressure showed no change in control, whereas that in patients who quit smoking increased at month 12 (69 ± 3 vs. 76 ± 3 mmHg, p < 0.01). The increase in HbA_1c at month 12 after quitting smoking correlated with body mass index before quitting smoking ( r  = 0.72, p < 0.005) and serum triglyceride before quitting smoking ( r  = 0.68, p < 0.01).
Conclusions:  Glycaemic control and diastolic blood pressure deteriorated in type 2 diabetic patients after quitting smoking. Type 2 diabetic patients who want to stop smoking need a caution to prevent deterioration of glycaemic control and blood pressure after quitting smoking.     

Long-term plasma levels of leptin and adiponectin in Rett syndrome

Objective  Rett syndrome is a progressive neurological disorder affecting almost exclusively females after age 6 months and characterised by acquired microcephaly, psychomotor retardation, growth failure, purposeless hand movements, autistic-like behaviour and wide-based and stiff legged gait. Leptin and adiponectin, peptides secreted by adipose tissue, are involved in the regulation of body weight and energy expenditure.
Design and patients  We investigated in patients with Rett syndrome the variations of plasma leptin and adiponectin and their relation over a 2-year period. Sixteen female patients, mean age at the basal time 9·4 ± 4·3 years, with classical Rett syndrome were enrolled. Controls were 16 healthy female subjects, mean age at the basal time 9·9 ± 3·4 years.
Measurements  Blood samples were withdrawn in the morning at the baseline, 12 months after and 24 months after; plasma leptin and adiponectin concentrations were detected by ELISA.
Results  In patients, leptin concentrations significantly increased, while adiponectin concentrations significantly decreased. Both leptin and adiponectin values were significantly higher than those found in controls at each time. Leptin significantly correlated with adiponectin in patients, while there was not a significant correlation in controls.
Conclusion  Since all patients were not obese, we might hypothesize that in Rett syndrome leptin and adiponectin might participate to clinical manifestations other than weight balance.     

Accelerated bone loss in post-menopausal women with mild primary hyperparathyroidism

OBJECTIVES Osteopenia is regarded as an indication for parathyroidectomy in primary hyperparathyroidism. However, uncertainty exists as to the extent and degree of the skeletal effects in those with mild disease. We sought to determine whether mild primary hyperparathyroidism affects the rate of bone loss in post-menopausal women.
DESIGN Prospective 2-year comparison of rates of bone loss throughout the skeleton in 17 post-menopausal women with untreated mild asymptomatic primary hyperparathyroidism, and 48 age-matched, eucalcaemic controls.
RESULTS The women with primary hyperparathyroidism had a greater annual rate of loss of bone mineral density (BMD) of the total body (mean ± SE, primary hyperparathyroidism −1.15 ± 0.31%, controls −0.39 ± 0.10%; P  = 0.04) and its spine subregion (primary hyperparathyroidism −2.08 ± 0.88%, controls 0.04 ± 0.35%; P  = 0.02). Lumbar spine BMD tended to decline in the primary hyperparathyroidism group (−0.35 ± 0.33%) in contrast to the control group (+ 0.28 ± 0.22%) ( P  = 0.10). There were no significant differences between the groups in rates of change of BMD in the legs or the proximal femur. In the primary hyperparathyroidism group, the rate of total body bone loss in the eight women known at study entry to have had long-standing (>5 years) primary hyperparathyroidism was −1.52 ± 0.61%/year, similar to that of the whole group.
CONCLUSION Primary hyperparathyroidism is associated with an increased rate of loss of total body bone mineral density in post-menopausal women. Prolonged disease duration is therefore likely to be associated with an increasing risk of osteopenia, such that skeletal surveillance and interventions designed to reduce bone loss should be considered.